Surface proteins play pivotal roles in physiological processes, including cell recognition, signal transduction, substance transport, and immune responses. However, challenges persist in characterizing abnormal surface proteins in disease states and identifying therapeutic targets, due to the low abundance of these proteins within the total proteome and the frequent presence of their complex glycosylation modifications. Recent years have witnessed the vigorous development of chemical proteomics, leading to the successful creation of various chemical probes for the labeling and characterization of cell surface proteins. These techniques have subsequently been applied to the detection of disease surface proteins and the discovery of corresponding targets. Surface protein characterization techniques based on chemical proteomics are discussed herein, focusing on the principles of amino acid-targeted labeling, proximity labeling, and glycoprotein capture. The novelty, advantages, and limitations of techniques such as targeted lysine labeling, peroxidase and photocatalytic proximity labeling, and chemical glycan capture and metabolic glycan labeling are elaborated, and their applications across various biological models and disease types are described, aiming to provide some reference for target discovery and drug development targeting surface proteins.

AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective To explore the application effect of isokinetic strength combined with conventional training in the rehabilitation after elbow joint release surgery.Methods A retrospective cohort study was conducted to analyze the clinical data of 82 patients who underwent elective elbow joint release surgery in our hospital from June 2022 to June 2023.They were divided into the control group and the observation group,with 41 cases in each group.Patients in the control group received routine training,while patients in the observation group received isokinetic strength training on the basis of the control group.The elbow joint function,elbow joint range of motion,pain degree,and ability of daily living before and after surgery of patients in the two groups were compared and analyzed.Results Three months after surgery,compared with the control group,the Mayo elbow function score of patients in the observation group were higher(P<0.05),the elbow flexion,extension,forearm supination,and forearm pronation ranges of motion of patients in the observation group were greater(P<0.05),the VAS score of patients in the observation group was lower(P<0.05),the ability of daily living of patients in the observation group was better(P<0.05).Conclusion The application of isokinetic strength combined with conventional training in elbow joint release surgery can promote elbow joint functional recovery,alleviate pain degree,and enhance ability of daily living.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Objective:To observe the effect of traditional chinese medicine fumigation combined with medicinal stick acupoint massage in patients with lumbar disc herniation(LDH).Methods:90 patients with LDH who were admitted to our hospital from March 2022 to March 2024 were divided into control group(received conventional treatment,n=45)and observation group(received traditional chinese medicine fumigation combined with acupuncture stick massage,n=45)by envelope drawing method.The clinical efficacy,lumbar range of motion,lumbar function[Japanese Orthopaedic Association Score(JOA),Oswestry Disability Index(ODI)],inflammatory cytokines[C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleukin-6(IL-6)],pain severity,and quality of life were compared between two groups.Results:Compared with control group after intervention,the observation group had higher clinical total effective rate,flexion,extension,scoliosis,straight legs Raise(SLR),JOA score,Quality of Life Assessment Scale(SF-36)score,and lower ODI score,Visual analogue Scale(VAS)score,ESR,CRP,and IL-6(P＜0.05).Conclusion:Application of traditional chinese medicine fumigation combined with medicinal stick acupoint massage in patients with LDH,it can reduce pain and inflammation,improve lumbar range of motion,lumbar function,and improve quality of life.

Objective:To explore the mediating effect of psychological resilience between perceived stress and job burnout among standardized gastroenterology nursing training students.Methods:A total of 156 nursing trainees who received standardized training in the Department of Gastroenterology at Shaanxi Provincial People's Hospital between December 2022 and July 2024 were selected by the convenience sampling method. Data were collected using a general information questionnaire, the Connor-Davidson Resilience Scale, the Chinese Perceived Stress Scale, and the Maslach Burnout Inventory-General Survey. A Pearson correlation analysis was used to examine the relationship among perceived stress, psychological resilience, and job burnout in standardized gastroenterology nursing training students. AMOS 24.0 statistical software was used to construct a structural equation model to analyze the mediating effect of psychological resilience between perceived stress and job burnout in standardized gastroenterology nursing training students. The bias-corrected bootstrap method was applied to test the mediating effect of psychological resilience.Results:The averaged total scores of 156 standardized gastroenterology nursing training students were (29.89±0.30) for perceived pressure, (62.45±2.44) for psychological resilience, and (57.85±3.44) for job burnout. Of the trainees, 88 (56.41%) exhibited job burnout, including 39 (25.00%) with mild burnout, 41 (26.28%) with moderate burnout, and 8 (5.13%) with severe burnout. The Pearson correlation analysis showed that perceived stress was positively correlated with job burnout ( r=0.543, P<0.05) and negatively correlated with psychological resilience ( r=-0.443, P<0.05), and psychological resilience was negatively correlated with job burnout ( r=-0.478, P<0.05). The results of bias-corrected bootstrap test showed that psychological resilience had a partial mediating effect between perceived stress and job burnout among standardized gastroenterology nursing training students ( P<0.05), accounting for 32.63% of the total effect. Conclusions:Moderate job burnout was observed in standardized gastroenterology nursing training students. Job burnout was closely related to perceived stress and psychological resilience. Psychological resilience partly mediated the relationship between perceived stress and job burnout. Therefore, clinical managers may alleviate the perceived psychological pressure and subsequently reduce the occurrence of job burnout among standardized nursing training students by increasing psychological resilience.

Aim To construct an mBSA/IL-1 β-induced inflam-matory monoarthritis model,and to explore the differences in the inflammatory monoarthritis mouse model induced by recombinant human IL-1 β and recombinant mouse IL-1 β combined with mB-SA,providing experimental evidence for the study of the patho-genesis and drug treatment of arthritis.Methods Twenty C57BL/6 mice were randomly divided into two groups,with the left knee joints as the model joints.One group was the mBSA+recombinant human IL-1β group(n=10),and the other was the mBSA+recombinant mouse IL-1β group(n=10).The de-gree of knee joint swelling and body weight changes in mice were observed.HE staining was used to detect the pathological chan-ges in the knee joints,and safranin O staining for the cartilage damage in the knee joints,and immunohistochemistry for the ex-pression of macrophages in the synovial tissue of the knee joints.Results Compared with the control joints(right knee joints),joint swelling occurred in the left knee joints of both groups of mice.Compared with the recombinant mouse IL-1β group,body weight of the mice in the recombinant human IL-1 β group de-creased more significantly,the pathology and cartilage damage of the knee joints were significantly higher,and the number of macrophages in the synovial tissue of the left knee joints in-creased significantly.Conclusion Recombinant human IL-1 βand recombinant mouse IL-1 β combined with mBSA induce in-flammatory monoarthritis in C57BL/6 mice.Compared with re-combinant mouse IL-1β,the arthritis induced by recombinant human IL-1β is more severe,suggesting that recombinant human IL-1β combined with mBSA is more conducive to the establish-ment of the inflammatory monoarthritis model.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.